1. PHARMACEUTICAL SUSPENSIONS AND EMULSIONS

2. Coarse Dispersions (Lyophobic colloids) Oil-in-water emulsions (o/w)
Suspension: Solid drug in liquid vehicle
Emulsion: Liquid drug in liquid vehicle:
Oil-in-water emulsions (o/w)
Water-in-oil (w/o)

3. Reasons for Use Drug is insoluble
Drug is more stable in suspension or emulsion
There is a need to control the rate of release of the drug
Drug has bad taste (oral)

4. Routes of Administration
Oral
Ocular
Otic
Rectal
Parenteral
Topical

5. I. Formulation of Suspensions

6. Wetting
Wetting agent

7. Well Formulated Suspension
Resuspend easily upon shaking
Settle rapidly after shaking
Homogeneous mix of drug
Physically and chemically stable during its shelf life
Sterile (parenteral, ocular)
Gets into syringe (parenteral, ocular)

8. “External” Forces Acting on Particles
Gravity
Brownian Movement
V(-o)g
Sedimentation equilibrium: Gravity is neutralized by Brownian movement
2-5 m

9. Settling and Aggregation
flock
The suspension shall form loose networks of flocks that settle rapidly, do not form cakes and are easy to resuspend.
Settling and aggregation may result in formation of cakes (suspension) that is difficult to resuspend or phase separation (emulsion)
cake

10. Sediment Volume F={volume of sediment Vu}/{original volume Vo} Vu Vo

11. DLVO: Optimal Distance
Energy
No flocks can form
Repulsion
Attraction
Attraction
Distance

12. Controlled Flocculation
Flocculating agent changes zeta-potential of the particles (it can be electrolyte, charged surfactant or charged polymer adsorbing on a surface).
If the absolute value of the zeta-potential is too high the system deflocculates because of increased repulsion and the dispersion cakes. + - +
Non-caking
Caking
Caking
F=Vu/Vo
Flocculating Agent - + + -
Zeta-potential

13. II. Formulation of Emulsions

14. Emulsification
Emulsifier

15. HLB and Use of Surfactants
Amphiphilic surfactants are characterized by the hydrophilic-lipophilic balance (HLB): a relative ratio of polar and non-polar groups in the surfactant
HLB ca. 1 to 3.5: Antifoams
HLB ca. 3.5 to 8: Water-in-Oil Emulsifiers
HLB ca. 7 to 9: Wetting and spreading agents
HLB ca. 8 to 16: Oil-in-Water Emulsifiers
HLB ca. 13 to 16: Detergents
HLB ca. 15 to 40: Solubilizers
HLB is an arbitrary parameter. Sometimes it is determined experimentally, for example, using reverse phase chromatography. There are numerous methods of computing of HLB. More information on computing of HLB (including blends of surfactants and requred HLB) can be found in: M. Stoklosa and H. Ansel, Pharmaceutical Calculations, Williams & Wilkins, Baltimore, 1996.

16. Required HLB
HLB needed for emulsification of the oil phase. If there are several oil ingredients the required HLB is calculated as a sum of their respective required HLB multiplied by the fraction of each.
Calculate the required HLB for the oil phase of the following o/w emulsion: cetyl alcohol 15 g., white wax 1g. Lanolin 2 g, emulsifier (q.s.), glycerin 5 g. water 100 g.
Required HLB Fraction
(from reference)
Cetyl alcohol 15 x 15/
White wax 12 x 1/18 0.7
Lanolin 10 x 2/18 1.1
Total required HLB
HLB is an arbitrary parameter. Sometimes it is determined experimentally, for example, using reverse phase chromatography. There are numerous methods of computing of HLB. More information on computing of HLB (including mixtures of surfactants) can be found in: M. Stoklosa and H. Ansel, Pharmaceutical Calculations, Williams & Wilkins, Baltimore, 1996.

17. HLB of Surfactant Blend
Surfactant blends are commonly used to obtain desired emulsifying properties.
What is the HLB of the mixture of 40 % Span 60 (HLB = 4.7) and 60 % Tween 60 (HLB = 14.9)?
HLB of mixture:
4.7 x x 0.6 = 10.8
In what proportion should Span 80 (HLB = 4.3) and Tween 80 (HLB = 15.0) be mixed to obtain “required” HLB of 12.0?
4.3.(1-x) + 15.x = 12 x = 0.72
72 % Tween 80 and 28 % Span 80
HLB is an arbitrary parameter. Sometimes it is determined experimentally, for example, using reverse phase chromatography. There are numerous methods of computing of HLB. More information on computing of HLB (including mixtures of surfactants) can be found in: M. Stoklosa and H. Ansel, Pharmaceutical Calculations, Williams & Wilkins, Baltimore, 1996.